Rescuing replication and osteogenesis of aged mesenchymal stem cells by exposure to a young extracellular matrix

Division of Research, Department of Comprehensive Dentistry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229-3900, USA.
The FASEB Journal (Impact Factor: 5.48). 04/2011; 25(5):1474-85. DOI: 10.1096/fj.10-161497
Source: PubMed

ABSTRACT This study aimed to determine whether aging negatively affects MSC replication and osteogenesis and whether these features could be altered by exposure to an extracellular matrix (ECM) generated by marrow cells from young or old mice. A cell-free ECM was prepared from cultured femoral marrow cells from either 3- or 18-mo-old C57BL/6 mice (young-ECM or old-ECM, respectively). The replication and osteogenesis of young or old MSCs maintained on young-ECM vs. old-ECM as well as plastic were examined in vitro and in vivo. We found that the frequency of MSCs in marrow from old mice, measured by colony-forming cells, was only marginally lower than that of young mice. In contrast, defects in the self-renewal and bone formation capacity of old MSCs were remarkable. These defects were corrected by provision of a young-ECM but not old-ECM. In parallel cultures maintained on a young-ECM, the intracellular levels of reactive oxygen species from both old and young mice were reduced 30-50% compared to those maintained on old-ECM or plastic. We concluded that aging negatively affects the formation of an ECM that normally preserves MSC function, and aged MSCs can be rejuvenated by culture on a young-ECM.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The development and application of decellularized extracellular matrices (ECM) has grown rapidly in the fields of cell biology, tissue engineering and regenerative medicine in recent years. Similar to decellularized tissues and whole organs, cell-derived matrices (CDM) represent bioactive, biocompatible materials consisting of a complex assembly of fibrillar proteins, matrix macromolecules and associated growth factors that often recapitulate, at least to some extent, the composition and organization of native ECM microenvironments. The unique ability to engineer CDM de novo based on cell source and culture methods makes them an attractive alternative to conventional allogeneic and xenogeneic tissue-derived matrices that are currently harvested from cadaveric sources, suffer from inherent heterogeneity, and have limited ability for customization. Although CDM have been investigated for a number of biomedical applications, including adhesive cell culture substrates, synthetic scaffold coatings, and tissue engineered products, such as heart valves and vascular grafts, the state of the field is still at a relatively nascent stage of development. In this review, we provide an overview of the various applications of CDM and discuss successes to date, current limitations and future directions.
    08/2014; 3(1). DOI:10.1039/C4BM00246F
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Odontogenesis is accomplished by reciprocal signaling between the epithelial and mesenchymal compartments. It is generally accepted that the inductive mesenchyme is capable of inducing the odontogenic commitment of both dental and non-dental epithelial cells. However, the duration of this signal in the developing dental mesenchyme and whether adult dental pulp tissue maintains its inductive capability remain unclear. This study investigated the contribution of growth factors to regulating the inductive potential of the dental mesenchyme. Human oral epithelial cells (OEs) were co-cultured with either human dental mesenchymal/papilla cells (FDPCs) or human dental pulp cells (ADPCs) under 2-dimensional or 3-dimensional conditions. Odontogenic-associated genes and proteins were detected by qPCR and immunofluorescence, respectively, and significant differences were observed between the two co-culture systems. The BMP7 and EREG expression levels in FDPCs were significantly higher than in ADPCs, as indicated by human growth factor PCR arrays and immunofluorescence analyses. OEs co-cultured with ADPCs supplemented with BMP7 and EREG expressed ameloblastic differentiation genes. Our study suggests that BMP7 and EREG expression in late bell-stage human dental papilla contributes to the inductive potential of dental mesenchyme. Furthermore, adult dental pulp cells supplemented with these two growth factors re-established the inductive potential of postnatal dental pulp tissue.
    Scientific Reports 05/2015; 5:9903. DOI:10.1038/srep09903 · 5.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adipose-derived stem cells (ASCs) can differentiate into multiple cell lineages and favor adipogenesis rather than osteogenesis. Because the extracellular matrix (ECM) component of the stem cell niche is important in stem cell differentiation, we hypothesized that ECM produced by human bone marrow stromal cells (BM-ECM) could enhance the osteogenic potential of ASCs during in vitro expansion. We have compared the replication and osteogenic differentiation of ASCs expanded on BM-ECM versus tissue culture plastic (TCP) in vitro and in vivo. During the first 2 passages, ASC proliferation on BM-ECM was 3.27-fold greater than that on TCP. ASCs expanded on BM-ECM formed more osteogenic colonies and higher expression of osteogenic markers than ASCs expanded on TCP. In nude mice, ASCs that had been expanded on BM-ECM formed more new bone tissue than those expanded on TCP. The data indicate that BM-ECM can be used to promote the osteogenic fate of ASCs.
    Cell Biology International 03/2015; 39(3). DOI:10.1002/cbin.10385 · 1.64 Impact Factor